Thrombin substrates suitable for use in coagulation assays are described in U.S. Pat. Nos. 3,884,896 and 4,640,893. A tableted form of thromboplastin having improved stability resulting from calcium separation is described in U.S. Pat. No. 4,755,461. A dry reagent consisting of thromboplastin and a thrombin substrate useful for liquid phase coagulation assays is described in U.S. Pat. No. 4,458,015.
An assay system for measuring glucose in blood, consisting of an inert porous matrix impregnated with reagents which produce a light-absorbing reaction, is described in U.S. Pat. No. 4,935,346. A blood sample is applied to one side of the matrix and reflectance measured on the opposite side. The membrane used in this system tends to rupture (lyse) red cells. This causes high levels of hemoglobin to permeate the interior of the membrane; and high levels of hemoglobin can be observed on the opposite side of the matrix. The '346 patent teaches that for analytes such as glucose, this effect may be overcome by using a particular chemistry that produces an optical signal with spectral properties that can be distinguished over the dominating spectra of this released hemoglobin, and reading the results with dual wavelength optics that correct for the hemoglobin spectra. Such an approach would not work for the very delicate, and hemoglobin sensitive, thrombin substrate coagulation chemistry. Another assay system suitable for measuring blood glucose, cholesterol, and urea is described in U.S. Pat. No. 4,774,192. The necessary reagents are impregnated in a structure, such as a porous membrane or bibulous film, which may be an asymmetric membrane. The '192 patent also suggests the use of flow control agents for controlling sample distribution in the structure.
U.S. Pat. Nos. 4,861,712, 4,910,510, and 5,059,525, describe multi-layer test articles suitable for monitoring blood coagulation. The '712 patent describes a complex structure consisting of a filamentous material, and a water soluble non-ionic polymer which coats and impregnates the filamentous material. This structure may contain thromboplastin and a detectable thrombin substrate, and is useful for monitoring a number of blood coagulation parameters, including prothrombin time.
The '525 patent describes a complex dry reagent for blood coagulation tests that contains a carrier material, and dried in it: a protease reactive to prothrombin (or Factors VII-X), a chromogenic protease substrate, a buffer, and a second coagulation factor. The inclusion of a protease into the dry reagent is useful for performing assays for coagulation factors, such as factor X, that must first be activated by proteolytic cleavage before their enzymatic activity can be measured.
U.S. Pat. No. 4,756,884, describes a capillary flow device for measuring blood characteristics, including prothrombin time.
The absorption and fluorescence emission spectra of (Cbz-Arg-NH).sub.2 --rhodamine are described in Leytus et al. (1983) Biochem J. 209:299-307.
Miale, Laboratory Medicine: Hematology, The C.V. Mosby Company, St. Louis, 4th Ed., 1972, pp. 599-602, teaches the absorption spectrum of hemoglobin.
Fluorescent substrates having long-wavelength emission spectra are described in Titus et al. (1982) J. Immunol. Meth. 50:193-204; Bigbee et al. (1978) Anal. Biochem. 88:114-122; and Burke and Orrenius (1978) Biochem. Pharmacol. (England), 27/11:1533-1538.
European Patent No. 574 134 describes a glucose or cholesterol test strip employing an asymetric membrane for receiving a blood sample.